Remyelination Regulated by microRNAs in Neurodegenerative Diseases： A Review / 中国实验方剂学杂志

Demyelination of the central nervous system often occurs in neurodegenerative diseases， such as multiple sclerosis （MS）. The myelin sheath， a layer of myelin membrane wrapping the axon， plays a role in the rapid conduction and metabolic coupling of impulses for neurons. The exposure of the axon will lead to axonal degeneratio， and further neuronal degeneration， which is the main cause of dysfunction and even disability in patients with demyelinating neurodegenerative diseases. In addition to the demyelination of mature myelin sheath， remyelination disorder is also one of the major reasons leading to the development of the diseases. The myelin sheath is composed of oligodendrocytes （OLs） derived from oligodendrocyte progenitor cells （OPCs） which are differentiated from neural stem cells （NSCs）. The process of myelin regeneration， i.e.， remyelination， is the differentiation of NSCs into OLs. Recent studies have shown that this process is regulated by a variety of genes. MicroRNAs， as important regulators of neurodegenerative diseases， form a complex regulatory network in the process of myelin regeneration. This review summarizes the main molecular pathways of myelin regeneration and microRNAs involved in this process and classifies the mechanisms and targets. This review is expected to provide a theoretical reference for the future research on the treatment of demyelinating diseases by targeting the regulation of microRNAs.

Enfermedad asociada a anticuerpos contra la glicoproteína de mielina de oligodendrocitos / Myelin oligodendrocyte glycoprotein antibody disease

Introducción: La enfermedad asociada a anticuerpos contra la glicoproteína de mielina del oligodendrocito (MOGAD, por sus siglas en inglés) es una entidad clínica recientemente identificada. La frecuencia de presentación del MOGAD es desconocida, pero se considera baja con respecto a otras enfermedades inflamatorias desmielinizantes. Materiales y métodos: Revisión narrativa de la literatura. Resultados: Las manifestaciones clínicas de esta condición son heterogéneas e incluyen neuritis óptica, mielitis, desmielinización multifocal del sistema nervioso central y encefalitis cortical. Se han descrito algunos hallazgos radiológicos que aumentan la sospecha diagnóstica, como el realce perineural del nervio óptico, el signo de la H en el cordón espinal y la resolución de lesiones T2 con el tiempo. El diagnóstico se basa en la detección de inmunoglobulinas G específicas contra MOG, en el contexto clínico adecuado. El tratamiento consiste en manejo de los ataques agudos con dosis altas de corticoides y en algunos casos se deberá considerar la inmunosupresión crónica, considerar la inmunosupresión crónica en pacientes con recurrencia o con discapacidad severa residual tras el primer evento. Conclusiones: En esta revisión narrativa se resumen los aspectos clave con respecto a la fisiopatología, las manifestaciones, el diagnóstico y el tratamiento de la MOGAD.

Introduction: The disease associated with antibodies against the myelin oligodendrocyte glycoprotein (MOGAD) is a recently identified clinical entity, with unknown frequency, but is considered low compared to other demyelinating inflammatory diseases. Materials And Methods: Narrative review. Results: The clinical manifestations are heterogeneous, ranging from optic neuritis or myelitis to multi-focal CNS demyelination or cortical encephalitis. There have been described characteristic MRI features that increase the diagnostic suspicion, such as perineural optic nerve enhancement, spinal cord H-sign or T2-lesion resolution over time. The diagnosis is based on the detection of specific G- immunoglobulins against MOG, in the suggestive clinical context. Acute treatment is based on high dose steroids and maintenance treatment is generally reserved for relapsing cases or patients with severe residual disability after the first attack. Conclusions: In this narrative review, fundamental aspects of pathophysiology, clinical and radiological manifestations, diagnosis and treatment of MOGAD are discussed.

Clinical spectrum of myelin oligodendrocyte glycoprotein antibody-associated disease in Brazil: a single-center experience / Espectro clínico de doença associada com anticorpos contra a glicoproteína de oligodendrócito de mielina no Brasil: uma experiencia de centro único

Abstract Background Anti-myelin oligodendrocyte glycoprotein (anti-MOG) antibody-associated disease (MOGAD) is an immune-mediated neurological disorder with a broad spectrum of clinical presentation that is often difficult to distinguish from other demyelinating diseases, such as multiple sclerosis and neuromyelitis optica spectrum disorder. Objective To describe the clinical and paraclinical characteristics of MOGAD in a Brazilian tertiary center. Methods We retrospectively reviewed the records of adult and pediatric patients who tested positive for anti-MOG antibodies and presented with clinical and radiological diseases compatible with MOGAD. Results Forty-one patients (10 children) were included: 56% female, 58% Caucasian, mean age at onset 31 years (range 6-64), with a mean disease duration of 59.6 months (range 1-264 months). The most frequent onset presentation was optic neuritis (68%), acute disseminated encephalomyelitis (ADEM, 12%), and myelitis (10%). A monophasic disease course was observed in 49%. EDSS median was 2.1 at the last visit. Most patients (83%) were under continuous immunosuppressive treatment. Azathioprine was the first-line treatment in 59%. In all ADEM cases, conus, and root involvement was radiologically observed on MRI. Conclusion Brazilian MOGAD patients presented with a similar spectrum of previously reported MOGAD phenotypes. Conus and spinal root involvement seems to be frequently present in MOGAD-ADEM and could serve as radiologic characteristics of this clinical entity.

Resumo Antecedentes A doença associada ao anticorpo da glicoproteína da mielina de oligodendrócitos (anti-MOG; MOGAD) é uma doença neurológica imunomediada com um amplo espectro de apresentações clínicas que muitas vezes é difícil de distinguir de outras doenças desmielinizantes, como a esclerose múltipla e o distúrbio do espectro da neuromielite óptica. Objetivo Descrever as características clínicas e paraclínicas da MOGAD em um centro terciário brasileiro. Métodos Revisamos retrospectivamente os prontuários dos pacientes adultos e pediátricos que testaram positivos para anticorpos anti-MOG e apresentaram um quadro clínico e radiológico compatível com MOGAD. Resultados Quarenta e um pacientes (10 crianças) foram incluídos: 56% do sexo feminino, 58% caucasianos, idade média de início da doença foi 31 anos (intervalo de 6-64), com duração média da doença de 59,6 meses (intervalo de 1-264 meses). A apresentação inicial mais frequente foi neurite óptica (68%), seguida pela encefalomielite disseminada aguda (ADEM, 12%) e mielite (10%). Um curso monofásico da doença foi observado em 49%. EDSS foi de 2,1 na última visita. A maioria dos pacientes (83%) estava sob tratamento imunossupressor contínuo. Azatioprina foi o tratamento de primeira linha em 59%. Em todos os casos de ADEM, o envolvimento do cone medular e das raízes espinhais foi observado radiologicamente na ressonância magnética. Conclusão Os pacientes brasileiros com MOGAD apresentam um espectro clínico e radiológico semelhante aos fenótipos de MOGAD relatados anteriormente. O envolvimento do cone e das raízes espinhais parece estar frequentemente presente no MOGAD-ADEM e poderia servir como característica radiológica nesta entidade.

AQP4-IgG NMOSD, MOGAD, and double-seronegative NMOSD: is it possible to depict the antibody subtype using magnetic resonance imaging? / NMOSD AQP4-IgG, MOGAD e NMOSD duplo soronegativo: é possível caracterizar o tipo de anticorpo pela ressonância magnética?

Abstract Background There is clinical and radiological overlap among demyelinating diseases. However, their pathophysiological mechanisms are different and carry distinct prognoses and treatment demands. Objective To investigate magnetic resonance imaging (MRI) features of patients with myelin-oligodendrocyte glycoprotein associated disease (MOGAD), antibody against aquaporin-4(AQP-4)-immunoglobulin G-positive neuromyelitis optica spectrum disorder (AQP4-IgG NMOSD), and double-seronegative patients. Methods A cross-sectional retrospective study was performed to analyze the topography and morphology of central nervous system (CNS) lesions. Two neuroradiologists consensually analyzed the brain, orbit, and spinal cord images. Results In total, 68 patients were enrolled in the study (25 with AQP4-IgG-positive NMOSD, 28 with MOGAD, and 15 double-seronegative patients). There were differences in clinical presentation among the groups. The MOGAD group had less brain involvement (39.2%) than the NMOSD group (p = 0.002), mostly in the subcortical/juxtacortical, the midbrain, the middle cerebellar peduncle, and the cerebellum. Double-seronegative patients had more brain involvement (80%) with larger and tumefactive lesion morphology. In addition, double-seronegative patients showed the longest optic neuritis (p = 0.006), which was more prevalent in the intracranial optic nerve compartment. AQP4-IgG-positive NMOSD optic neuritis had a predominant optic-chiasm location, and brain lesions mainly affected hypothalamic regions and the postrema area (MOGAD versus AQP4-IgG-positive NMOSD, p= 0 .013). Furthermore, this group had more spinal cord lesions (78.3%), and bright spotty lesions were a paramount finding to differentiate it from MOGAD (p = 0.003). Conclusion The pooled analysis of lesion topography, morphology, and signal intensity provides critical information to help clinicians form a timely differential diagnosis.

Resumo Antecedentes Há sobreposição clínica e radiológica entre as doenças desmielinizantes. No entanto, seus mecanismos fisiopatológicos são diferentes e apresentam prognósticos e demandas de tratamento distintos. Objetivo Investigar as características de imagens de RM dos pacientes com doença associada à glicoproteína de oligodendrócito de mielina (MOGAD), a doenças do espectro da neuromielite óptica positivas para antiaquaporina-4 imunoglobulina G (AQP4-IgG NMOSD), e pacientes duplamente soronegativos. Métodos Estudo retrospectivo e transversal para analisar as características e frequência das lesões do sistema nervoso central (SNC). Dois neurorradiologistas avaliaram consensualmente as imagens do cérebro, das órbitas e da medula espinhal. Resultados Ao todo, foram incluídos 68 pacientes(25 com AQP4-IgG NMOSD, 28 com MOGAD e 15 duplo-soronegativos). Há diferenças na apresentação clínica entre os grupos. O grupo MOGAD demonstrou menor frequência de comprometimento do cérebro (39.2%) comparado com o AQP4-IgG NMOSD (p = 0.002), com predomínio da distribuição das lesões nas regiões subcortical/justacortical, mesencéfalo, pedúnculos cerebelares médios e cerebelo. O grupo duplo-soronegativo demonstrou maior frequência de comprometimento do cérebro (80%), com lesões de maiores dimensões e com morfologia tumefeita, além de neurite óptica com maior extensão (p = 0.006). O grupo AQP4-IgG NMOSD demonstrou neurite óptica com predomínio na região óptico-quiasmática e as lesões encefálicas acometeram predominantemente as regiões hipotalâmica e área postrema (MOGAD versus AQP4-IgG NMOSD p = 0.013). Além disso, foram observadas mais lesões na medula espinhal (78.3%) e a presença da "bright spotty lesion" foi um achado primordial para a sua diferenciação com os pacientes MOGAD (p = 0.003). Conclusão A análise pormenorizada das características das lesões por RM dos pacientes com doenças desmielinizantes imunomediadas fornece informações fundamentais que auxiliam os médicos no diagnóstico diferencial em um momento oportuno.

Myelin oligodendrocyte glycoprotein antibody-associated optic neuritis: an update / Neurite óptica associada com anticorpo contra a glicoproteína oligondendrócita da mielina: uma breve atualização

ABSTRACT Myelin oligodendrocyte glycoprotein-immunoglobulin G (IgG)-associated optic neuritis has been established as a new entity of immune-mediated optic neuropathy. Patients usually present with recurrent optic neuritis, often bilaterally with initially severe vision loss and optic disc edema. However, in contrast to aquaporin 4-IgG-seropositive neuromyelitis optica spectrum disorder, visual recovery tends to be more favorable, with good response to steroid treatment. Another important differential diagnosis of myelin oligodendrocyte glycoprotein-IgG--associated optic neuritis is multiple sclerosis. Close monitoring for signs of relapse and long-term immunosuppression may be considered to maintain optimal visual function. The diagnosis can be made on the basis of the presence of a specific, usually serological, antibody against myelin oligodendrocyte glycoprotein (IgG; cell-based assay), and a demyelinating event (optic neuritis, myelitis, brainstem syndrome, or cortical lesions with seizures). The clinical spectrum of this newly recognized inflammatory demyelinating disease is expanding rapidly. We briefly review the epidemiological characteristics, clinical manifestations, diagnostic considerations, and treatment options of myelin oligodendrocyte glycoprotein-IgG-associated optic neuritis.

RESUMO A neurite óptica associada à glicoproteína de oligodendrócito de mielina-IgG foi estabelecida como uma nova entidade de neuropatia óptica imunomediada. Tipicamente os pacientes apresentam neurite óptica recorrente, muitas vezes bilateral, com perda de visão frequentemente severa e alta prevalência de edema do disco óptico na fase aguda. No entanto, em contraste com neuromyelitis optica spectrum disorder associada com presença de anticorpo contra aquaporina 4, a recuperação visual tende a ser mais favorável e responde bem ao tratamento com corticoide em altas doses. A esclerose múltipla representa outro importante diagnóstico diferencial de glicoproteína de oligodendrócito de mielina-IgG. O diagnóstico pode ser feito com base na presença de um anticorpo específico, geralmente sorológico contra glicoproteína de oligodendrócito de mielina (IgG, ensaio baseado em células), e presença de evento desmielinizante (neurite óptica, mielite, síndrome do tronco cerebral, lesões corticais com convulsões). O espectro clínico desta doença desmielinizante inflamatória recém-reconhecida está se expandindo rapidamente. Faremos uma breve revisão das características epidemiológicas, manifestações clínicas, considerações diagnósticas e opções de tratamento da neurite óptica associada à glicoproteína de oligodendrócito de mielina-IgG.

Progress of the central nervous system myelin sheath development and related diseases in children / 国际儿科学杂志

The myelin sheath of the central nervous system(CNS)is a multilayer lipid membrane with oligodendrocyte membrane surrounding the axon.The development of myelin sheath in children follows the corresponding laws of time and space, and this process of myelination is considered to be related to children′s proper behavior and function.The myelin sheath development of CNS in childhood is a multi-step and extremely complex process, and the integrity of myelin sheath plays a crucial role in shaping CNS function.At present, it has been found that many neurological diseases in children, such as multiple sclerosis, transverse myelitis and pediatric optic neuritis are closely related to myelin sheath abnormality.Therefore, this paper reviews the progress of myelin sheath development and related diseases in childhood, so as to provide a basis for clinical diagnosis and treatment of myelin sheath abnormalities.

Enhancement of oligodendrocyte autophagy alleviates white matter injury and cognitive impairment induced by chronic cerebral hypoperfusion in rats

Cognitive impairment caused by chronic cerebral hypoperfusion (CCH) is associated with white matter injury (WMI), possibly through the alteration of autophagy. Here, the autophagy-lysosomal pathway (ALP) dysfunction in white matter (WM) and its relationship with cognitive impairment were investigated in rats subjected to two vessel occlusion (2VO). The results showed that cognitive impairment occurred by the 28th day after 2VO. Injury and autophagy activation of mature oligodendrocytes and neuronal axons sequentially occurred in WM by the 3rd day. By the 14th day, abnormal accumulation of autophagy substrate, lysosomal dysfunction, and the activation of mechanistic target of rapamycin (MTOR) pathway were observed in WM, paralleled with mature oligodendrocyte death. This indicates autophagy activation was followed by ALP dysfunction caused by autophagy inhibition or lysosomal dysfunction. To target the ALP dysfunction, enhanced autophagy by systemic rapamycin treatment or overexpression of Beclin1 (BECN1) in oligodendrocytes reduced mature oligodendrocyte death, and subsequently alleviated the WMI and cognitive impairment after CCH. These results reveal that early autophagy activation was followed by ALP dysfunction in WM after 2VO, which was associated with the aggravation of WMI and cognitive impairment. This study highlights that alleviating ALP dysfunction by enhancing oligodendrocyte autophagy has benefits for cognitive recovery after CCH.

Neuromyelitis optica spectrum disorders: a review with a focus on children and adolescents / Espectro da neuromielite óptica: uma revisão com ênfase em crianças e adolescentes

Abstract Neuromyelitis optica spectrum disorder (NMOSD) is a rare and severe inflammatory disorder of the central nervous system (CNS). It is strongly associated with anti-aquaporin 4 antibodies (AQP4-IgG), and it mainly affects young women from non-white ethnicities. However, ~ 5 to 10% of all cases have onset during childhood. Children and adolescents share the same clinical, radiologic, and laboratory presentation as adults. Thus, the same NMOSD diagnostic criteria are also applied to pediatric-onset patients, but data on NMOSD in this population is still scarce. In seronegative pediatric patients, there is a high frequency of the antibody against myelin oligodendrocyte glycoprotein (MOG-IgG) indicating another disease group, but the clinical distinction between these two diseases may be challenging. Three drugs (eculizumab, satralizumab, and inebilizumab) have been recently approved for the treatment of adult patients with AQP4-IgG-positive NMOSD. Only satralizumab has recruited adolescents in one of the two pivotal clinical trials. Additional clinical trials in pediatric NMOSD are urgently required to evaluate the safety and efficacy of these drugs in this population.

Resumo O espectro da neuromielite óptica (ENMO) é uma rara e grave doença inflamatória do sistema nervoso central (SNC), fortemente associada ao anticorpo anti-aquaporina 4 (AQP4-IgG) e que afeta preferencialmente mulheres jovens de etnias não-caucasianas. No entanto, aproximadamente de 5 a 10% de todos os casos se iniciam na infância. Crianças e adolescentes compartilham as mesmas características clínicas, radiológicas e laboratoriais dos adultos. Além disso, o mesmo critério diagnóstico de ENMO é aplicado para pacientes com início na infância. No entanto, dados da população pediátrica são escassos. Em pacientes pediátricos soronegativos, existe uma alta frequência de positividade ao anticorpo contra a glicoproteína na mielina do oligodendrócito (MOG-IgG), indicando outra patologia; porém, a distinção clínica entre as duas doenças é desafiadora. Três medicações (eculizumabe, inebilizumabe e satralizumabe) foram recentemente aprovadas para pacientes adultos com AQP4-IgG. Apenas um dos ensaios pivotais do satralizumabe recrutou adolescentes. Novos ensaios clínicos em pacientes pediátricos com ENMO são necessários para avaliar a segurança e eficácia destas drogas nesta população.

Changes of corneal nerve fiber and the correlation analysis with visual acuity in demyelinating optical neuritis patients / 中华眼底病杂志

Objective:To investigate the changes in the nerve fiber layer of the cornea in patients with demyelinating optic neuritis (DON) and its correlation with visual acuity.Methods:A cross-sectional study. From March 2021 to July 2022, 27 cases (39 eyes) of DON patients diagnosed in the Department of Neurology and Ophthalmology of Beijing Tongren Hospital Affiliated to Capital Medical University were enrolled in this study. According to the serological test results, the patients were divided into aquaporin 4 antibody associated optic neuritis (AQP4-ON group) and myelin oligodendrocyte glycoprotein antibody associated optic neuritis (MOG-ON group), with 15 cases (19 eyes) and 12 cases (20 eyes) respectively. According to previous history of glucocorticoid treatment, the patients were divided into glucocorticoid treated group and non-glucocorticoid treated group, with 17 cases (27 eyes) and 10 cases (12 eyes) respectively. Twenty healthy volunteers (20 eyes) with age- and gender-matched were selected as the control group. All eyes underwent best corrected visual acuity (BCVA) and in vivo confocal microscopy (IVCM) examinations. BCVA was performed using Snellen's standard logarithmic visual acuity chart, which was converted into logarithmic minimum angle resolution (logMAR) visual acuity during statistics. The corneal nerve fiber length (CNFL), corneal nerve fiber density (CNFD), corneal nerve fiber branch length (CNBL), corneal nerve fiber branch density (CNBD) and the density of corneal dendritic cells (DC) were detected by IVCM examination. Parameter comparison between groups by t-test and Kruskal-Wallis rank sum test. The correlation between logMAR BCVA and pamameters of corneal nerve fibers were analyzed using Spearman analysis. Results:The CNFL, CNFD, and CNBL of the DON group and the control group were (10.67±2.55) mm/mm 2, (57.78±12.35) root/mm 2, (3.27±1.34) mm/mm 2, and (13.74±3.05) mm/mm 2, (70.95±13.14) root/mm 2, and (4.22±1.03) mm/mm 2, respectively; the difference in CNFL, CNFD, and CNBL between the two groups were statistically significant ( t=4.089, 3.795, 2.773; P<0.05). The CNFL, CNBL, and CNBD of the affected eyes in the MOG-ON group and AQP4-ON group were (12.02±2.13) mm/mm 2, (3.80±1.19) mm/mm 2, (47.97±8.86) fibers/mm 2, and (9.25±2.19) mm/mm 2, (2.72±1.19) mm/mm 2, (39.43±13.86) fibers/mm 2, respectively; the differences in CNFL, CNBL, and CNBD between the two groups were statistically significant ( t=-4.002, -2.706, -2.306; P<0.05). The corneal DC density of the patients in the hormone treated group and the non-hormone treated group was (24.43±8.32) and (41.22±9.86) cells/mm 2, respectively. The difference in corneal DC density between the two subgroups was statistically significant ( P<0.001). Correlation analysis showed that there was a significant negative correlation between logMAR BCVA and CNBL and CNFL in patients with DON ( r=-0.422, -0.456; P<0.05). Conclusions:There are different degrees of corneal nerve fiber damage in patients with different types of DON. There was a negative correlation between BCVA and the length of corneal nerve fibers.

Anti-myelin oligodendrocyte glycoprotein-IgG associated disorders coexisting with brucellosis: a case report and literature review / 中华神经科杂志

Objective:To study the clinical characteristics and prognosis of Brucella and other pathogens infections complicated with anti-myelin oligodendrocyte glycoprotein-IgG associated disorders (MOGAD). Methods:The clinical data of a patient with brucellosis complicated with MOGAD diagnosed in the Department of Neurology of the First Affiliated Hospital of Zhengzhou University in April 2022 were reported, and related case reports of infection coexisting with MOGAD were reviewed and summarized.Results:This case was a 44-year-old male, with recurrent fever and anorexia, followed by sudden weakness, numbness, pain in both lower limbs and dysuria, and then pain in the right neck. Magnetic resonance imaging showed lesions in the spine and spinal cord. Due to the positive myelin oligodendrocyte glycoprotein antibodies in cerebrospinal fluid and serum, and the growth of Brucella in blood culture, he was diagnosed as brucellosis complicated with MOGAD. After anti-brucellosis and glucocorticoid therapy, his symptoms improved. The literature on infection coexisting with MOGAD was reviewed and 22 cases were included. The infection sources included COVID-19, Borrelia burgdorferi, etc. No case of Brucella infection complicated with MOGAD had been reported. The main clinical manifestations of the 22 cases included myelitis (63.6%, 14/22), optic neuritis (40.9%, 9/22), acute disseminated encephalomyelitis (18.2%, 4/22), multiphasic disseminated encephalomyelitis (4.5%, 1/22) and meningoencephalitis (4.5%, 1/22). Magnetic resonance imaging was performed in 20 cases, showing spinal cord lesions in 12 cases (60.0%, 12/20), intracranial lesions in 10 cases (50.0%, 10/20) and optic nerve lesions in 6 cases (30.0%, 6/20). Cerebrospinal fluid examination was performed in 19 patients, of whom 13 (13/19) had increased cerebrospinal fluid cell count and 10 (10/18) had increased cerebrospinal fluid protein. Twenty-two patients received glucocorticoid therapy, of which 95.5% (21/22) responded well and 95.5% (21/22) had a good prognosis. Conclusions:Brucella and other pathogens infection may complicate with MOGAD, with similar clinical manifestations, and glucocorticoid therapy is effective.

Roles of NG2 Glia in Cerebral Small Vessel Disease / 神经科学通报·英文版

Cerebral small vessel disease (CSVD) is one of the most prevalent pathologic processes affecting 5% of people over 50 years of age and contributing to 45% of dementia cases. Increasing evidence has demonstrated the pathological roles of chronic hypoperfusion, impaired cerebral vascular reactivity, and leakage of the blood-brain barrier in CSVD. However, the pathogenesis of CSVD remains elusive thus far, and no radical treatment has been developed. NG2 glia, also known as oligodendrocyte precursor cells, are the fourth type of glial cell in addition to astrocytes, microglia, and oligodendrocytes in the mammalian central nervous system. Many novel functions for NG2 glia in physiological and pathological states have recently been revealed. In this review, we discuss the role of NG2 glia in CSVD and the underlying mechanisms.

Coordinated Regulation of Myelination by Growth Factor and Amino-acid Signaling Pathways / 神经科学通报·英文版

Myelin-forming oligodendrocytes in the central nervous system (CNS) and Schwann cells in the peripheral nervous system (PNS) are essential for structural and functional homeostasis of nervous tissue. Albeit with certain similarities, the regulation of CNS and PNS myelination is executed differently. Recent advances highlight the coordinated regulation of oligodendrocyte myelination by amino-acid sensing and growth factor signaling pathways. In this review, we discuss novel insights into the understanding of differential regulation of oligodendrocyte and Schwann cell biology in CNS and PNS myelination, with particular focus on the roles of growth factor-stimulated RHEB-mTORC1 and GATOR2-mediated amino-acid sensing/signaling pathways. We also discuss recent progress on the metabolic regulation of oligodendrocytes and Schwann cells and the impact of their dysfunction on neuronal function and disease.

Differential diagnosis of demyelinating diseases: what's new? / Diagnóstico diferencial das doenças desmielinizantes: o que há de novo?

ABSTRACT Background: Acquired demyelinating disorders lead to overlapping visual, pyramidal, sensory, autonomic, and cerebellar deficits and may lead to severe disability. Early diagnosis and start of treatment are fundamental towards preventing further attacks and halting disability. Objective: In this paper we provide an updated overview of the differential diagnoses of acquired demyelinating disorders. Methods: We performed a critical targeted review of the diagnoses of the most prevalent demyelinating disorders: multiple sclerosis (MS), neuromyelitis optica spectrum disorders (NMOSD) and myelin oligodendrocyte glycoprotein antibody disease (MOGAD). Results: We discuss the workup, diagnostic criteria and new biomarkers currently being used for the diagnosis of these disease entities taking into account the particularities of the Brazilian population and healthcare system. Conclusion: A comprehensive analysis of medical history, physical examination, biomedical and imaging data should be performed to obtain differential diagnosis. Diagnostic criteria should be mindfully employed considering ethnic and environmental particularities of each patient.

RESUMO Antecedentes: Doenças desmielinizantes adquiridas levam a déficits visuais, piramidais, sensitivos, autonômicos e cerebelares que se sobrepõem e podem conduzir a grave incapacidade. O diagnóstico e o início de tratamento precoces são fundamentais para a prevenção de surtos e ocorrência de incapacidade. Objetivo: Neste artigo, apresentamos uma visão geral atualizada sobre o diagnóstico diferencial de doenças desmielinizantes adquiridas. Métodos: Realizamos uma revisão crítica sobre o diagnóstico das doenças desmielinizantes mais prevalentes: esclerose múltipla (EM), doença do espectro neuromielite óptica (NMOSD) e doença associada ao anticorpo contra a glicoproteína da mielina do oligodendrócito (MOGAD). Resultados: Discutimos a investigação, os critérios diagnósticos e os novos biomarcadores atualmente empregados para o diagnóstico dessas doenças, levando em conta as particularidades da população e sistema de saúde brasileiros. Conclusão: Uma análise minuciosa do histórico médico, exame neurológico e exames biomédicos e de imagem deve ser realizada para se fazer um diagnóstico diferencial de doença desmielinizante. Critérios diagnósticos devem ser empregados cautelosamente considerando-se particularidades étnicas e ambientais de cada paciente.

COVID-19-associated optic neuritis – A case series and review of literature

Neuroophthalmic manifestations are very rare in corona virus disease?19 (COVID?19) infection. Only few reports have been published till date describing COVID?19?associated neuroophthalmic manifestations. We, hereby, present a series of three cases who developed optic neuritis during the recovery period from COVID?19 infection. Among the three patients, demyelinating lesions were identified in two cases, while another case was associated with serum antibodies against myelin oligodendrocyte glycoprotein. All three patients received intravenous methylprednisolone followed by oral steroids according to the Optic Neuritis Treatment Trail ptotocol. Vision recovery was noted in all three patients, which was maintained at 2 months of the last follow up visit

Clinical profile, imaging features and short term visual outcomes of Indian optic neuritis patients with and without seromarkers for myelin oligodendrocyte glycoprotein and neuromyelitis optica

Purpose: To analyze clinical profile, imaging features, and short?term visual outcomes of optic neuritis patients in Indian population with and without seromarkers for myelin oligodendrocyte glycoprotein (MOG)/neuromyelitis optica (NMO). Methods: Electronic medical records of 203 optic neuritis patients who presented between June 2018 and December 2019 to the Neuro?ophthalmology services of a tertiary care center in India were retrospectively analyzed. Results: Of 203 patients, 57 patients (28.08%) were positive for MOG?antibody and 20 patients (9.85%) were positive for NMO antibody. 114 patients (56.16%) were double?negative (negative for both antibodies) and 12 patients (5.91%) were diagnosed as multiple sclerosis (MS). None of the patients had both antibodies. Mean age of presentation was 31.29 ± 1.035 years. There was female preponderance in NMO?optic neuritis (NMO?ON) and MS?optic neuritis (MS?ON) groups (1:5). Mean vision on presentation was worse (logMAR 1.570 ± 0.863) in NMO?ON group. The mean visual acuity showed statistically significant recovery (logMAR 0.338 ± 0.639) in the final follow?up in MOG?optic neuritis (MOG?ON) group. Multivariate logistic regression analysis revealed poor visual outcome in patients presenting with retrobulbar neuritis, optic disc pallor, bilateral sequential optic nerve involvement, and with positive NMO antibody. Optic neuritis patients presenting with disc edema associated with pain and positive for MOG antibody were found to have a better visual outcome. Conclusion: In this Indian optic neuritis cohort, the prevalence of MOG?ON was higher than NMO?ON. MOG?ON had a better visual outcome than NMO?ON. The incidence of MS?ON was less compared to the western literature. A significant number of patients (114 patients, 56.16%) were double negative for both seromarkers and yet had presented with optic neuritis with no clinical or imaging features suggestive of MS/MOG associated disease (MOG AD)/NMO spectrum disorder (NMO SD).

Advances in myelin oligodendrocyte glycoprotein antibody-associated disease / 国际儿科学杂志

Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is one of inflammatory demyelinating disorders of the central nervous system.Due to the diverse and atypical clinical manifestations, positive rate of current detection methods is not high, and early diagnosis is difficult.This review aims to elucidate the research progress of the epidemiology, pathogenesis, clinical characteristics, diagnostic criteria, biological markers, treatment and prognosis of MOGAD, in order to improve the understanding of MOGAD for clinicians, so as to identify, treat and reduce the recurrence of MOGAD as early as possible.

Myelin-oligodendrocyte glycoprotein antibody-associated disease / 中华神经科杂志

Myelin-oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is a recently-established autoimmune central nervous system demyelinating disease, characterized by the detection of serum anti-myelin-oligodendrocyte glycoprotein antibody of IgG1 type. Sharing similar clinical manifestations with multiple sclerosis and aquaporin-4 antibody positive neuromyelitis optica spectrum disorder, it has yet demonstrated a unique disease course, pathological and radiological features. Therefore, MOGAD should be regarded as a disease entity to carry out further investigation. This review intends to summarize its pathogenesis, diagnosis and treatment progresses, so as to provide guidance for clinical practice.

A case of limbic encephalitis with positive anti-leucine-rich glioma inactivated 1 protein antibody and anti-myelin oligodendrocyte glycoprotein antibody / 中华神经科杂志

A case of limbic encephalitis with positive anti-leucine-rich glioma inactivated 1 protein (LGI1) antibody and anti-myelin oligodendrocyte glycoprotein (MOG) antibody was reported. The patient was a middle-aged male with a history of retinal vein occlusion. The main symptoms were temporal lobe epilepsy, facial arm dystonia, autonomic nerve dysfunction. Magnetic resonance imaging showed long T 2 signal in the right hippocampus without enhancement and normal perfusion. Electroencephalogram showed paroxysmal slow wave and sharp slow wave in interictal period. Blood anti-MOG antibody, blood and cerebrospinal fluid anti-LGI1 antibody were double positive. The main diagnosis was limbic encephalitis. After treatment with hormone and gamma globulin, the symptoms were improved and double antibodies were turned negative. Anti-LGI1/MOG double positive cases are rare, and the clinical manifestations and imaging manifestations of double positive antibody cases are not completely consistent with those with each single antibody, with different characteristics. This report can help clinicians enhance awareness.

Developmental Origins of Human Cortical Oligodendrocytes and Astrocytes / 神经科学通报·英文版

Human cortical radial glial cells are primary neural stem cells that give rise to cortical glutaminergic projection pyramidal neurons, glial cells (oligodendrocytes and astrocytes) and olfactory bulb GABAergic interneurons. One of prominent features of the human cortex is enriched with glial cells, but there are major gaps in understanding how these glial cells are generated. Herein, by integrating analysis of published human cortical single-cell RNA-Seq datasets with our immunohistochemistical analyses, we show that around gestational week 18, EGFR-expressing human cortical truncated radial glial cells (tRGs) give rise to basal multipotent intermediate progenitors (bMIPCs) that express EGFR, ASCL1, OLIG2 and OLIG1. These bMIPCs undergo several rounds of mitosis and generate cortical oligodendrocytes, astrocytes and olfactory bulb interneurons. We also characterized molecular features of the cortical tRG. Integration of our findings suggests a general picture of the lineage progression of cortical radial glial cells, a fundamental process of the developing human cerebral cortex.

Analysis of influencing factors related to the prognosis of visual acuity on myelin oligodendrocyte glycoprotein antibody positive optic neuritis after methylprednisolone pulse / 中华眼底病杂志

Objective:To analyze the prognostic factors of vision of myelin oligodendrocyte glycoprotein (MOG) antibody positive associated optic neuritis (ON) after methylprednisolone pulse therapy.Methods:A clinical observational study. A total of 32 patients (47 eyes) with MOG antibody positive ON were observed and followed up in the ophthalmology department of Beijing Tongren Hospital Affiliated to Capital Medical University and Beijing Puren Hospital from March 2019 to January 2022. Clinical data including the best corrected visual acuity (BCVA) and orbital magnetic resonance imaging were recorded. The BCVA was examined by Snellen visual acuity chart, which was finally converted into the logarithm of the minimal angle of resolution (logMAR) for statistical analysis. There were 22 case (38 eyes) with complete image data. All patients were treated with intravenous methylprednisolone pulse (IVMP) for 3-5 days. According to the intervention time (from onset to glucocorticoid treatment), the patients were divided into three groups: <7 d group, 7-14 d and> 14 d group, with 16, 13, 11 eyes, respectively. The median follow-up time was 28 months. After 1 week, 1, 3 and 6 months treatment, the same equipment and methods were used for relevant examinations to observe the changes of visual acuity and the factors influencing the prognosis of visual acuity after IVMP treatment. Logistic regression and linear regression were used to analyze the prognostic correlation factors. Receiver operating characteristic (ROC) curve was used to determine the critical cut-off point of intervention timing.Results:Among the patients, 16 were male and 16 were female. The median onset age was 26 years. The onset duration time was 5-60 days. There were 18 cases (56.3%, 18/32) with abnormal serum immune indexes. The initial symptom was decreased vision with unilateral or bilateral ON. Seventeen (53.1%, 17/32) cases had unilateral ON and 15 (46.9%, 15/32) cases with bilateral ON. Thirty-six eyes (76.6%, 36/47) got optic disc edema, 37 eyes (78.7%, 37/47) accompanied by pain of ocular movement. The nadir logMAR BCVA was mean 1.69±0.13. Long T2WI signals with segmental thickening in the orbital segment of the optic nerve were obtained in 27 eyes (71.1%, 27/38) and in 24 eyes (63.2%, 24/38) with optic nerve and sheath enhancement. During the follow-up period, there were 10 cases of relapse (31.3%, 10/32). The logMAR BCVA of attacked eyes were 0.52±0.09, 0.22±0.06, 0.12±0.06, 0.10±0.06 at 1 week and 1, 3 and 6 months after IVMP treatment, respectively. The rate of BCVA improvement was the fastest at 1 week after treatment, and BCVA returned to stability at 3 months. Logistic regression analysis showed that the timing of intervention was significantly correlated with the prognosis of vision in primary onset patients (odds ratio=12.17, P=0.006), with a negative linear regression relationship ( r=-0.48, 95% confidence interval -0.71--0.17, P=0.008). Comparing the logMAR BCVA between the intervention time >14 group with the <7 group and the 7-14 group, there were statistically significant difference ( P=0.017, 0.037), respectively. The cut-off point of ROC curve to predict the optimal intervention time was 13.5 days. Other factors such as: gender, age, predisposing factor, pain of eye motion, edema of optic disc, bilateral ON, imaging changes, abnormal autoimmune indicators were not associated with the prognosis of visual acuity. Conclusion:The timing of hormone intervention in primary onset patients is an important factor affecting the prognosis of vision and the optimal intervention time window of IVMP is two weeks.